Dr Brona Murphy received funding through the NCRC’s Paediatric Research Project Grant scheme for the project “Improving and personalizing chemotherapy treatment options for paediatric brain tumour patients”. Results from the project were recently published in the journal “Cell Death and Disease”.
In a paper entitled “The identification of BCL-XL and MCL-1 as key anti-apoptotic proteins in medulloblastoma that mediate distinct roles in chemotherapy resistance”, Dr Marie Claire Fitzgerald, Dr Murphy and colleagues at the Royal College of Surgeons in Ireland show that targeting the anti-apoptotic proteins BCL-XL and MCL-1 could be a promising new way to treat medulloblastoma, a cancer accounting for 15-20% of cases of paediatric brain cancer.
You can read Brona’s summary of the article below.
Medulloblastoma, a common brain cancer in children, often requires harsh treatments like radiation therapy, which can cause life-altering side effects. Our research group in the RCSI explores ways to make chemotherapy that targets this cancer more effective so that reliance on radiation could potentially be decreased. In this newly-published study, we looked at certain proteins involved in the process of cell death, known as apoptosis, to see if they could predict how well medulloblastoma cells respond to chemotherapy.
We found that one particular protein, called BCL-XL is critical in helping cancer cells resist chemotherapy. When this protein is present, it prevents the cancer cells from dying. We showed that inhibiting this protein with another drug could make chemotherapy drugs like cisplatin more effective against medulloblastoma cells, especially those that typically resist treatment.
Additionally, we were interested in testing if the BCL-XL inhibitor was effective at killing medulloblastoma cells by itself. However, we found that when BCL-XL is inhibited, another protein, MCL-1, steps up as a backup to prevent cell death. So, for the best results, both proteins should be targeted. We suggest that drugs which inhibit these proteins could be a promising new way to treat medulloblastoma. This approach might allow for reduced use of radiation therapy and improve treatment outcomes for children with this type of cancer.